Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

El tejido adiposo, ¿solo un almacén de energía? / Adipose Tissue, Just an Energy Storage?

Resumen Cuando los alimentos cubren los requerimientos energéticos, el organismo almacena el exceso de calorías como glucógeno en el hígado y el músculo, y los triacilgliceroles en el tejido adiposo. Morfológica y funcionalmente se clasifica en blanco y pardo. El pardo tiene gran cantidad de mitocondrias, almacena los triacilgliceroles en vacuolas y disipa la energía en forma de calor; el blanco almacena energía en gotas lipídicas que ocupan la mayor parte de su volumen. Después de la ingesta de alimentos se libera insulina, lo que hace que externen GLUT4 para absorber glucosa. Los quilomicrones o las lipoproteínas de muy baja densidad (VLDL) transportan los triacilgliceroles a los depósitos de tejido adiposo. Durante el ayuno, por acción del glucagón, se liberan enzimas que degradarán a los tri, di y monogliceroles para liberar a los ácidos grasos. El tejido adiposo libera citocinas pro y antiinflamatorias, así como leptina, adiponectina que regulan el apetito y la saciedad. La proteína cinasa activada por AMP se activa como respuesta a una baja en la cantidad de energía de la célula y le ayuda a mantener un balance energético. En el adipocito promueve la degradación de los triacilgliceroles para liberar a los ácidos grasos que se emplearán como fuente energética. Se requiere de mayor cantidad de estudios para conocer más sobre la función del tejido adiposo como regulador del metabolismo y no solo como almacén de energía.

Abstract When food meets energy requirements, the body stores in the liver and in the muscle the excess of calories as glycogen and triacylglycerols in the adipose tissue. Morphologically and functionally, it is classified into white and brown tissues. Brown tissue has many large mitochondria and stores triacylglycerols in vacuoles and dissipates energy as heat; white tissue stores energy as lipid droplets that occupy most of the adipocyte's volume. After food intake insulin is released, which causes GLUT4 externalization into the cellular membrane to absorb glucose. Chylomicrons or VLDL transport triacylglycerols to adipose tissue depots. During fasting, by the action of glucagon, enzymes are released that will degrade tri-, di- and mono-glycerols to release fatty acids. Adipose tissue releases pro and anti-inflammatory cytokines, as well as leptin and adiponectin that regulate appetite and satiety. AMPK is activated in response to a decrease in the cell's energy and helps it to maintain its energetic balance. In the adipocyte, it promotes the degradation of triacylglycerols releasing fatty acids to be used as an energy source. More studies are needed to learn more about the function of adipose tissue as a regulator of the metabolism and not only as an energy storage.

A comprehensive morphometric study of visceral and subcutaneous adipose tissue depots in mice, hamsters and rats / Un estudio morfométrico completo de los depósitos de tejido adiposo visceral y subcutáneo en ratones, hámsters y ratas

SUMMARY: Adipose tissue morphology of different fat tissue depots can be described using the number of adipocytes and cell surface of adipocytes. This study deals with characteristics and morphometric analysis of white and brown adipose tissue depots in healthy adult laboratory mice, hamsters and rats of both sexes. The number of unilocular adipocytes in white adipose tissue differs from one adipose tissue depot to another, with the largest number of adipocytes in mice and a similar number in hamsters and rats. The smallest surface area and the largest percentage of small unilocular adipocytes were found in mice. White adipose tissue in hamsters and rats was predominantly made out of a larger percentage of medium-sized adipocytes and a smaller percentage of small and medium-sized adipocytes. Uncoupling protein 1 positive multilocular adipocytes were found in classic brown adipose tissue depots with larger percentages in mice (93.20 %) and hamsters (91.30 %), while rats had a smaller percentage (78.10 %). In white and brown adipose tissue, significant differences between species and both sexes within the same species were found, indicating the influence of sexual dimorphism. The presented morphometric results could serve as a basis for further studies concerning experimental animal models of metabolic disorders and obesity.

RESUMEN: La morfología del tejido adiposo de diferentes depósitos de tejido graso se puede describir utilizando el número de adipocitos y la superficie celular de los adipocitos. Este estudio analiza las características y el análisis morfométrico de los depósitos de tejido adiposo blanco y marrón en ratones, hamsters y ratas de laboratorio, adultos sanos de ambos sexos. El número de adipocitos uniloculares en el tejido adiposo blanco difiere de un depósito de tejido adiposo a otro, con el mayor número de adipocitos en ratones y un número similar en hámsteres y ratas. La superficie más pequeña y el mayor porcentaje de adipocitos uniloculares pequeños se encontraron en ratones. El tejido adiposo blanco en hámsteres y ratas estaba compuesto predominantemente por un mayor porcentaje de adipocitos de tamaño mediano y un porcentaje menor de adipocitos de tamaño pequeño y mediano. Los adipocitos multiloculares positivos para la proteína desacopladora 1 se encontraron en depósitos de tejido adiposo marrón clásico con mayores porcentajes en ratones (93,20 %) y hámsters (91,30 %), mientras que las ratas tenían un porcentaje menor (78,10 %). En el tejido adiposo blanco y pardo se encontraron diferencias significativas entre especies y entre ambos sexos dentro de una misma especie, lo que indica la influencia del dimorfismo sexual. Los resultados morfométricos presentados podrían servir como base para futuros estudios sobre modelos animales experimentales de trastornos metabólicos y obesidad.

Mice as an animal model for the study of adipose tissue and obesity / Ratones como modelo animal para el estudio del tejido adiposo y la obesidad

SUMMARY: The study of adipose tissue has gained increasing importance in the biomedical area due to its implications for health and obesity. Obesity is a situation of great concern mainly in the Western world due to its high prevalence and morbidity. Experimental studies on obesity often need a model where it is possible to carry out experiments, drug testing, and other therapeutic procedures, which are typically not possible in humans. Although several animals are used for obesity studies, rodents are by far the most used animals, and among rodents, mice are particularly indicated for this investigation. This mini review will introduce the challenging classification of obesity in rodents, paralleling human obesity, defining and classifying what an obese mouse is. The text will differentiate between white adipose tissue (WAT, aimed at endocrine secretion and lipogenesis) and brown adipose tissue (BAT, aimed at thermogenesis) and describe the browning process of white adipocytes in an adaptation to increase thermogenesis. The text will also describe the various types of body fat in mice with their differences and indications for investigation and teach how to recognize and dissect these fats. At the end of this introductory reading, the young researcher is expected to have acquired sufficient knowledge to start an experimental investigative project on obesity.

RESUMEN: El estudio del tejido adiposo ha ganado una importancia creciente en el área biomédica por sus implicaciones para la salud y la obesidad. La obesidad es una situación de gran preocupación, principalmente, en el mundo occidental debido a su alta prevalencia y morbilidad. Los estudios experimentales sobre la obesidad a menudo necesitan un modelo en el que sea posible realizar experimentos, pruebas de drogas y otros procedimientos terapéuticos, que normalmente no son posibles en humanos. Aunque se utilizan varios animales para estudios de obesidad, los roedores son, con mucho, los animales más utilizados y, entre los roedores, los ratones están especialmente indicados para esta investigación. Esta mini revisión presenta la desafiante clasificación de la obesidad en roedores, en paralelo con la obesidad humana, definiendo y clasificando qué es un ratón obeso. El texto diferencia entre tejido adiposo blanco (WAT, destinado a la secreción endocrina y lipogénesis) y tejido adiposo marrón (BAT, destinado a la termogénesis) y describe el proceso de pardeamiento de los adipocitos blancos en una adaptación para aumentar la termogénesis. El texto también describe los diversos tipos de grasa corporal en ratones con sus diferencias e indicaciones para la investigación y enseña cómo reconocer y diseccionar estas grasas. Al final de esta lectura introductoria, se espera que el joven investigador haya adquirido los conocimientos suficientes para iniciar un proyecto de investigación experimental sobre la obesidad.

Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from

Molecular mechanism of Gegen Qinlian Decoction in promoting differentiation of brown adipose tissue to improve glucose and lipid metabolism disorders in diabetic rats / 中国中药杂志

This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.

Quantification of Fat Concentration and Vascular Response in Brown and White Adipose Tissue of Rats by Spectral CT Imaging

Recent developments in natural products for white adipose tissue browning / 中国天然药物

Excess accumulation of white adipose tissue (WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke, heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige (brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue (BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products (alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes (T2DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

Effect of Yinfupian and Yangfupian on Brown Adipose Tissue of Yang Deficiency Mice / 中国实验方剂学杂志

Objective:To observe the expression of brown adipose tissue (BAT), cells, proteins and corresponding genes in Yang deficiency model mice induced by Rhei Radix et Rhizoma suspension, and to explore the thermogenesis of processed products of Aconiti Lateralis Radix Praeparata with Jianchang faction characteristics. Method:Twenty mice, half male and half female, were randomly selected as the normal female and male groups. And the other 80 mice were administrated with Rhei Radix et Rhizoma suspension (the content of 0.25 g·mL-1) to establish Yang deficiency model, after the model was established, they were randomly divided into the model female and male groups, female and male groups of Shengfupian, female and male groups of Yinfupian, female and male groups of Yangfupian, 10 mice in each group. Mice were intragastric administrated with corresponding medical solution for two weeks (1.54 g·kg-1·d-1) according to groups. Normal group and model group were given equal volume distilled water. After administration, BAT of scapular region of mice was collected and the changes of BAT cells were observed by hematoxylin-eosin (HE) staining. The expression of uncoupling protein 1 (UCP1) and its mRNA were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with the normal group of the same sex, the proportion of BAT in the model group decreased significantly (P<0.01). Compared with the model group of the same sex, the proportion of BAT in female mice from Shengfupian and Yinfupian groups increased significantly (P<0.01), while there was no significant difference between each administration group and model group in the male mice. Compared with normal mice of the same sex, there were many scattered vacuoles in BAT cells of the model group, and fewer cells could be observed due to larger vacuoles. Compared with the model group of the same sex, BAT cells in mice from the Shengfupian group showed fewer vacuoles, smaller cells and tight arrangement, the density of BAT cells in mice from the Yangfupian group also increased significantly, while the vacuoles in BAT cells of mice from the Yinfupian group decreased relatively and the cells did not increase significantly. Compared with the same sex mice, the expression level of UCP1 in the model group and the normal group was statistically significant (P<0.05, P<0.01). In the female mice, the expression level of UCP1 in Yangfupian group was significantly higher than that in the model group (P<0.05), each administration group of male mice was significantly different from that of the model group of the same sex (P<0.05), of which Yangfupian was the most significant. The relative expression of UCP1 mRNA in the model group was significantly lower than that in the normal group of the same sex (P<0.05, P<0.01). In the female mice, compared with the model group, the relative expression levels of UCP1 mRNA in Yangfupian group, Shengfupian group and Yinfupian group increased significantly (P<0.05, P<0.01), compared with Yangfupian group, the relative expression levels of UCP1 mRNA in Shengfupian and Yinfupian were also significantly different (P<0.05). In the male mice, compared with the model group, the relative expression of UCP1 mRNA in Yangfupian group was significantly increased (P<0.01), but there was no significant difference in Shengfupian group and Yinfupian group, in addition, compared with Yangfupian group, the relative expression of UCP1 mRNA in Shengfupian group and Yinfupian group had significant difference (P<0.05). Conclusion:Shengfupian, Yinfupian and Yangfupian all have obvious improvement on Yang deficiency syndrome induced by Rhei Radix et Rhizoma suspension. The mechanism may be to promote the expression of UCP1 protein and its mRNA and enhance the activity of BAT. And the effect of Yangfupian is the best.

Wntless represses brown adipose tissue differentiation and energy expenditure / 中华内分泌代谢杂志

Objective To explore the effect of Wntless ( Wls)-mediated Wnt signaling on the development and energy metabolism of brown adipose tissue (BAT). Methods BAT-specific Wls knockout (WlsMyf5Δ/Δ) mice were generated by Cre-loxP system. The differentiations of BAT in WlsMyf5Δ/Δ knockout mice and Wlsfl/fl control mice were analyzed by histological morphology, immunohistochemistry, real-time PCR, and Western blot. After stromal vascular fraction (SVF) cells in BAT were induced to differentiate, oil red O staining, real-time PCR, and cell respiration experiments were performed for analyzing in-vitro cell differentiation and oxygen consumption. The energy metabolism of mice was monitored by rectal temperature, oxygen consumption rate in BAT, and energy expenditure. The adiposity of mice was evaluated by NMR while the glucose metabolism was analyzed by the glucose and insulin tolerance tests. Results The WlsMyf5Δ/Δ knockout mice appeared smaller body size, lower weight, higher percentage of lean fat, lower size of BAT, with higher body temperature on the back as compared to Wlsfl/fl control mice. The differentiation and thermogenesis of BAT in Wls-deficient mice were relatively augmented, along with an increase in Ucp1 mRNA and protein expressions. SVF cells from BAT in WlsMyf5Δ/Δ knockout mice revealed enhanced brown differentiation. Adiposity was decreased and glucose metabolic capacity was enhanced in the WlsMyf5Δ/Δknockout mice, without significant change in the whole body. Conclusion Wls-mediated Wnt signaling decreases the thermogenesis and glucose metabolism of BAT by suppressing its differentiation.

Effects of caloric restriction on the expression of lipocalin-2 and its receptor in the brown adipose tissue of high-fat diet-fed mice

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

Research progress on the mutual effects between brown adipose tissue and bone / 中华内分泌代谢杂志

Brown adipose tissue (BAT) increases energy consumption by directly dissipating stored energy in the form of heat through the role of uncoupling protein (UCP1). Recent studies have found that brown adipocytes may also regulate metabolism through autocrine, paracrine, and endocrine mechanisms. A growing body of evidences have shown that the BAT has a close relationship with bone metabolism, in which BAT secretes a variety of factors to regulate bone metabolism, while bone also secretes a variety of bioactive substances to control BAT function. In addition, BAT may indirectly participate in bone metabolism through muscle-mediated regulation or SNS activity and improvement of body metabolism, thus forming a BAT-skeletal axis. In this paper, we try to explain the relationship between brown adipose tissue and bone, and to discuss their interactive mechanisms.

Effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet / 中国药理学通报

Aim: To observe the effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet. Methods: Male 8-week-old C57BL/6J mice were randomly divided into HFD + 5 °C group and HFD + RT group, after 8 weeks of high-fat diet. Male 8-week-old C57BL/6J mice were randomly divided into normal + 5 °C group and normal + RT group, after 8 weeks of normal diet. Each group of mice were intervened for 2 h at different temperatures in the same time period for 8 weeks. Parameters, including body weight, food intake, inguinal white adipose tissue (iWAT) mass, brown adipose tissue (BAT) mass, blood glucose, blood lipids, leptin, adiponectin, adipose tissue pathology and in situ expression of uncoupling protein 1(UCP1) and prohibitin protein (PHB) in iWAT and BAT. Results: Compared with HFD + RT group, cold exposure not only significantly reduced body weight, blood glucose, iWAT weight/body weight ratio, TC, TG, LDL-C and leptin, but also increased food intake and BAT weight in high-fat diet mice. HE staining showed that iWAT and BAT cells became smaller and had multiple compartments. The iWAT had a browning trend. Immunohistochemistry showed that UCP1 and PHB protein in iWAT and BAT significantly increased. Conclusions: Cold exposure can counteract the weight gain caused by a high-fat diet, which may be related to the activation of brown adipose tissue and the induction of browning of white adipose tissues, increasing heat production and reducing white fat accumulation.

Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia / 医学前沿

Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.

Effects and mechanism of hypoxia exposure on related genes in brown fat tissue of obese mice based on mRNA expression profile microarray / 中国应用生理学杂志

OBJECTIVE@#This study intended to screen differentially expressed genes and pathways in Brown Adipose Tissue (BAT) of obese mice after the intervention of hypoxia by mRNA expression profile microarray, exploring the mechanism of hypoxia activated BAT.@*METHODS@#Thirty C57BL/6J male mice were divided into the normal diet control group (N, =8), high-fat diet control group (OB, =8) and high-fat diet hypoxia group (H, =8). Group H was intervened by hypoxia exposure in the oxygen concentration of 11.2% of the normal oxygen and hypoxia for 8 h/d, 6 d/w of 4 weeks. Blood lipid and blood glucose were detected after intervention; RNA microarray scan and bioinformation analysis were done of BAT from scapula. Genes significantly ( ≤ 0.05) regulated more than 1.5 fold were chosen to do Gene Ontology and enrichment analysis by KOBAS 2.0, and confirmation of genes participating in key biological process (BP) and pathway was done by real time qPCR.@*RESULTS@#After intervention, the body weight and blood lipid and glucose levels in group H were significantly lower than those of group OB. Comparing with group N, 802 genes were significantly up-regulated and 1 175genes were down-regulated. The BP of these genes mainly concerned with glucose and lipid metabolic process and inflammatory reaction. Comparing with group OB, 297 genes were significantly up-regulated and 228 genes were down-regulated. These genes participated in glucose and lipid metabolic process, lipid transport, muscle system process and cardiovascular system development. The pathways of regulating BAT by hypoxia exposure mainly concentrated on the HIF-1, PI3K-AKT, FoxO and ErbB signaling pathways.@*CONCLUSIONS@#A series of genes and pathways in BAT could be adjusted by hypoxia exposure, so that hypoxia could improve the activity of BAT, promoting obese organism to lose weight.

Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of erythropoietin (EPO) on blood glucoseand plasma insulin level, index of insulin resistance (HOMA-IR), introperitoneal glucose tolerance test (IPGTT), the mRNA and protein level of PR domain-containing 16 (PRDM16), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), fibroblast growth factor 21 (FGF21) of brown adipose tissue (BAT) in mice fed with high fat diet (HFD) in order to provide clues for the mechanism of obesity and complication.@*METHODS@#Twenty C57BL/6J male mice fed with HFD were randomly divided into control group (HFD-Con) and EPO group (HFD-EPO), mice in the two groups were injected intraperitoneally normal saline and EPO (200 IU/kg) res pectively, 3 times per week for consecutive 4 weeks.Then the body weight, blood glucose, plasma insulin level, HOMA-IR and IPGTT were detected.The mRNA and protein level of PRDM16, FGF21, p-STAT3/STAT3 in brown adipose tissue were detected by real-time quantitative RT-PCR and Western blot respectively.@*RESULTS@#After intraperitoneal injection of EPO for 4 weeks, the body weight of the mice in HFD-EPO and HFD-Con groups was (26.65±0.85) g and (31.50±1.6 0) g respectively.The blood glucose of the mice in HFD-EPO group[(62.79±8.09) mg/dl]was significantly decreased compared with that in HFD-Con group[(91.06±9.86) mg/dl].The plasmainsulin level in HFD-EPO group[(10.56±1.06)μU/ml]was significantly decreased compared with that in HFD-Con group[(13.2±1.1)μU/ml, < 0.01].The level of IPGTT in HFD-EPO group was significantly ameliorated and th e HOMA-IR decreased compared with those in HFD-Con group.The mRNA and protein expressions of PRDM16, FGF21 and the level of STAT3 of brown adipose tissue in HFD-E PO group were increased obviously.And there was no difference of FGF21 mRNA content in liver and FGF21 content in plasmabetween the two groups.@*CONCLUSIONS@#EPO could promote differentiation of brown adipose tissue by increase in the express ion of PRDM16, and decrease the blood glucose level, ameliorate glucose metabolism in obses mice.

Brown adipose tissue thermogenesis and energy metabolism / 体力科学

Obesity and diabetes have become a major epidemic problem. Preventing obesity has proven a challenge because this would require increased physical activity and/or reduced energy intake; both of which are difficult to enforce. Brown adipose tissue (BAT) is a major metabolic organ that contributes to the regulation of energy metabolism in small rodents. In humans, since its rediscovery in 2009, BAT has emerged as a potential target to fight obesity and related metabolic diseases such as type 2 diabetes. The BAT of humans is activated by acute cold exposure and mediates cold-induced thermogenesis. The metabolic activity of BAT demonstrates huge individual variation and is negatively associated with body fat accumulation and glucose intolerance. The decreased BAT can be reactivated and recruited by repeated cold exposure, which has the effects of increasing thermogenesis and decreasing body fat. Such effects of cold exposure can be mimicked by oral ingestion of some food ingredients with agonistic activity at temperature-sensitive transient receptor potential channels. To develop strategies to boost BAT thermogenesis for obesity prevention, more insight is needed into the physiological significance of human BAT and mechanisms by which BAT function is regulated by aging, as well as endogenous and environmental factors. This review will summarize the current knowledge on the activation of human BAT thermogenesis and its roles in obesity-related disorders.

Bone marrow adipose tissue——A kind of special adipose tissue / 中华内分泌代谢杂志

Bone marrow adipose tissue (MAT) is formed by the accumulation of adipocytes in the bone marrow cavity. Previously, the function of MAT is mainly considered to be filled with bone marrow cavity for the mechanical support. However,with the in-depth study of MAT,it has been gradually understood that MAT is not only a part of the bone marrow microenvironment,may also be a new endocrine "organ". The main component of bone marrow adipocytes(BMA) plays a regulatory role in bone marrow and systemic metabolism through the autocrine and paracrine secretion of adiponectin, leptin, interleukin-6, and a series of cytokines. Though its biological characteristics are somewhat similar with white fat adipose tissue(WAT) and brown adipose tissue(BAT),there are some significant differences,so MAT is thought to be a special adipose tissue. MAT is also involved in the development of hematological diseases,metabolic diseases,degenerative diseases,and may affect their outcomes. MAT may be the auxiliary diagnostic criteria and treatment targets of such diseases. This article will review the MAT's own biological characteristics,the differences and associations among three types of adipose tissue and the link between MAT and the diseases,which aims to explore the new research direction through the profound understanding of MAT.